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Canine Mendelian disease record

Degenerative Myelopathy (DM)

Degenerative Myelopathy (DM). Autosomal recessive (incomplete penetrance). Observed in 138 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,641 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier
OMIA:000263-9615
Autosomal recessive (incomplete penetrance)
Linked gene
SOD1
Human counterpart
In humans, this gene is SOD1. OMIM 147450 In people, SOD1 appears tolerant of loss-of-function variation (gnomAD v4.1 constraint, LOEUF 1.51). Constraint measures intolerance to loss-of-function only and does not indicate importance; some tolerant genes cause disease through other mechanisms. In people, variants in the SOD1 gene have conflicting classifications in ClinVar, and none is expert-reviewed. The evidence is unsettled, not that variants here are benign.
Source dataset
Sniff Atlas v1.0.1 / DOI
The plain version

Degenerative Myelopathy (DM) is a progressive condition that affects the spinal cord, leading to gradual loss of coordination and mobility in dogs. It primarily impacts the nervous system, causing weakness and difficulty walking over time.

How it is inherited. DM is inherited in an autosomal recessive way with incomplete penetrance, meaning a dog needs two copies of the gene variant to be at risk, but not all dogs with two copies will develop the condition.

This condition is found in several breeds including Cavalier King Charles Spaniels, Boxers, Bernese Mountain Dogs, German Shepherds, Yorkshire Terriers, and Australian Cattle Dogs.

Being a carrier is not the same as being affected; it’s worth asking your vet about testing if you have one of these breeds to better understand your dog's genetic health.

Carrier rates in well-studied breeds
  • Cavalier King Charles Spaniel · 51%
  • Boxer · 42%
  • Bernese Mountain Dog · 26%
  • German Shepherd · 20%
  • Yorkshire Terrier · 13%
  • Australian Cattle Dog · 5%

Educational carrier context from the Sniff disease layer (Donner 2023 (carrier) + substrate; educational, not diagnostic). Not a diagnosis and not a prediction about your dog. See the full carrier chart below for sample sizes and the Donner cohort when available.

Context source: Donner 2023 (carrier) + substrate; educational, not diagnostic · dataset doi:10.5281/zenodo.20566358 . We would rather give you a short plain summary with a receipt than invent comfort.

The human connection

A model of human amyotrophic lateral sclerosis type 1

Dogs with this condition carry a change in SOD1. In people, changes in the same gene cause amyotrophic lateral sclerosis type 1. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In humans it is also called: ALS1, FALS, amyotrophic lateral sclerosis 1, amyotrophic lateral sclerosis 1, familial, amyotrophic lateral sclerosis, familial.

MONDO:0007103 OMIM 105400OMIM 618598

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Closely related human conditions exist for this gene. Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

This is an adult onset degeneration of the spinal cord that progresses to paraplegia and tetraparesis. There is no successful treatment. A genetic test is available. A different mutation in the SOD1 gene causes an early onset disease: OMIA:002322-9615 : Dyskinesia, paroxysmal, SOD1-related in Canis lupus familiaris.

Clinical features

Most dogs are at least 8 years of age at the onset of clinical signs, which include hyporeflexia, upper motor neuron proprioceptive spasticity and ataxia in the pelvic limbs. Widespread limb muscle atrophy can be observed and the disease progresses to paraplegia and eventually flaccid tetraparesis (Awano et al., 2009). Hyperesthesia, cranial nerve signs (e.g. difficulty in swallowing and barking), urinary and fecal incontinence (Coates et al., 2010) can be observed and in final stages of the disease respiratory muscles fail (Nardone et al., 2016). There is no effective treatment. [IT thanks DVM student Jane Lai for contributions to this entry in April 2022].

Molecular genetics

The first likely causative variant described is a G to A transition (c.118G>A; p.E40K) in exon 2 of SOD1. All affected dogs tested were homozygous mutant. However, some homozygous mutant dogs had no signs of degenerative myelopathy, which suggests incomplete penetrance or other causative loci (Awano et al., 2009). The mutation is hypothesized to lead to SOD1 aggregation, as cytoplasmic inclusions in affected dogs stain with anti-SOD1 antibodies (Awano et al., 2009). A second causal mutation (c.52A>T; p.Thr18Ser) in the same gene, in a Bernese Mountain Dog, was reported by Wininger et al. (2011). Having genotyped 408 Bernese Mountains dogs for both the above mutations, Pfahler et al. (2014) reported that "The c.118G>A mutation was heterozygous in 188 (46.1%) and homozygous in 27 (6.6%) BMD (Table S2). The c.52A>T mutation was heterozygous in 65 (15.9%) and homozygous in two (0.5%) dogs. Twenty-two of the animals had both SOD1 mutations heterozygous (5.4%). The haplotype analysis for all BMD revealed no haplotype with both mutated alleles on a single chromosome (Figs S1 and S2). Therefore, these 22 dogs are likely to be compound heterozygous for the SOD1 haplotypes AA and TG." One of the 22 compound heterozygotes showed clinical signs of degenerative myelopathy. Summarising all available evidence, Pfahler et al. (2014) concluded that "compound heterozygosity [for the two mutations] may confer a similar risk to DM like the c.118G>A homozygous mutation". Ivansson et al. (2016) reported "that variations in SP110-mediated gene transcription may underlie, at least in part, the variability in risk for developing DM among PWCs that are homozygous for the disease-related SOD1 mutation" Mandrioli et al. (2021) reported that "three [affected Hovawart] dogs were homozygous for the c.118A allele, but none had the SP110 'risk' haplotype, suggesting a weak association of SP110 with the onset of DM in this breed. Our data suggest that the Hovawart breed is predisposed to the SOD1:c.118G>A mutation, which is associated with the development of DM."

Pathology

Histopathologic examination of the spinal cord is necessary for definitive diagnosis. Noninflammatory axonal and myelin degeneration is present at all levels of the spinal cord, being most severe in the dorsal lateral funiculus within the middle to caudal thoracic region. Segmental axonal and myelin degeneration, endoneurial fibrosis, hypomyelinated fibers and secondary demyelination are present in peripheral nerves. Axon cylinder vacuolization is characteristic (Coates et al., 2010).

Prevalence

In an extensive project, Zeng et al. (2014) genotyped 33,747 dogs representing 222 breeds for both known mutant alleles, namely c.52T and c.118A. They concluded that "the SOD1:c.118A allele is widespread and common among privately owned dogs whereas the SOD1:c.52T allele is rare and appears to be limited to Bernese Mountain Dogs." Full details are available in the paper. Mizukami et al. (2016) reported the frequency of the c.118A allele as 0.008 in 500 Border collies in Japan. Regarding the insertion reported by Turba et al. (2107), these authors reported that "The allele containing the insertion was highly prevalent in Hovawart dogs, accounting for the 26.6% of allele frequency. The insertion was also found in other unrelated breeds such as Rough Collies and Standard Poodles." Santos et al. (2020) genotyped 97 German Shepherd dogs for the SOD1:c.118G>A mutation using a PCR/RFLP test. The dogs were located in Brazil and had no clinical signs of degenerative myelopathy at the time of sampling. They “observed genotype frequencies (with 95% confidence interval) of: 0.758 (0.672-0.844), 0.242 (0.156-0.328) and 0.000 (0.000-0.000) for "GG", "AG" and "AA" genotypes, respectively.” Maki et al. (2022) genotyped 541 German Shepherd Dogs (GSD) registered with the Japanese GSD Registration Society from 2000 to 2019, for the SOD1:c.118G>A likely causal variant (omia.variant:36). They reported "330 G/G dogs (61%), 184 G/A dogs (34%), and 27 A/A dogs (5%), indicating a frequency of the mutant allele of 0.220". For each of the seven A/A dogs over 10 years old (this being an adult-onset disease), the owners reported "DM-related clinical signs, indicating a clinical progression rate of 100%".

Control

Due to the high frequency of the causative mutation in Boxers and Pembroke Welsh Corgis, in these breeds it is not practical to exclude carriers from breeding, so it is recommended that carriers be bred to noncarriers. Breeding of affected dogs of any breed should be avoided.

Genetic testing

Investigating the "many discordant findings between the parental and the offspring genotypes found by different laboratories" in testing for the c.118G>A variant, Turba et al. (2017) discovered "An insertion of 54 nucleotides [in the SOD1 gene] composed of a poly-T stretch and 15 nucleotides containing the duplication of the exon 2-intron 2 junction was . . . responsible for the partial mismatch of the reverse primer used for a direct sequencing assay. The mismatch hampered the amplification of the corresponding allele and caused an evident drop-out effect. The insertion is in complete linkage disequilibrium with the c.118G allele." Santos et al. (2020) identified “a deletion of one “T” in the position 26540247 described as ENSCAFG00000008859:g.26540247del … located in the intron 1 of the SOD1 gene. … Although the role of the ENSCAFG00000008859:g.26540247del on structure and expression of SOD1 (and consequently its relationship with CDM) was not investigated in this study, its location does not suggest that it can influence the expression of the studied disease.” However, this variant prevented in a small number of dogs adequate genotyping of the SOD1:c.118G>A in the PCR-RFLP test used in this study.

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 105400 Disease · OMIM 618598 Gene · OMIM 147450

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:000263-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 69.

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for Degenerative Myelopathy (DM) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A
Parent B
NNClear
NmCarrier
NmCarrier
mmAffected
Clear25%
Carrier50%
Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.
Your breed

See what Degenerative Myelopathy (DM) looks like in your dog's breed.
Carrier frequency by breed

Top 25 well-sampled breeds (n ≥ 50)

Maximum per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%50%100%
Fox Terrier Wire82.4% · n 182
Pembroke Welsh Corgi53.3% · n 4,364
Cavalier King Charles Spaniel51.0% · n 2,242
Boxer42.1% · n 4,552
Bernese Mountain Dog26.2% · n 955
Pug26.0% · n 5,154
Chesapeake Bay Retriever25.4% · n 138
Tibetan Terrier23.7% · n 95
American Eskimo Dog23.5% · n 302
Bloodhound22.5% · n 280
Soft Coated Wheaten Terrier21.1% · n 607
German Shepherd20.4% · n 15,645
Cardigan Welsh Corgi19.6% · n 125
French Bulldog19.6% · n 13,111
Shih Tzu17.1% · n 7,527
n = 55,279 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas
Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Degenerative Myelopathy (DM) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Fox Terrier Wire 82.4% 182
Pembroke Welsh Corgi 53.3% 4,364
Cavalier King Charles Spaniel 51.0% 2,242
Boxer 42.1% 4,552
Bernese Mountain Dog 26.2% 955
Pug 26.0% 5,154
Chesapeake Bay Retriever 25.4% 138
Tibetan Terrier 23.7% 95
American Eskimo Dog 23.5% 302
Bloodhound 22.5% 280
Soft Coated Wheaten Terrier 21.1% 607
German Shepherd 20.4% 15,645
Cardigan Welsh Corgi 19.6% 125
French Bulldog 19.6% 13,111
Shih Tzu 17.1% 7,527
Biewer Terrier 14.9% 184
Finnish Lapphund 14.9% 57
Parson Russell Terrier 14.1% 181
Boykin Spaniel 13.6% 154
Yorkshire Terrier 13.0% 8,367
Airedale Terrier 12.8% 200
Bulldog Standard 12.7% 4,816
Collie 12.6% 1,207
Miniature Pinscher 11.2% 658
Presa Canario 9.4% 64

Top 25 of 102 well-sampled breeds with at least one observed carrier shown.

▸ Also observed in 36 small-sample breeds (n < 50)

Frequencies in this section are statistical estimates with wide Wilson 95% confidence intervals (typically >20 percentage points). Treat these as "carriers observed but the true population frequency is not yet measurable" rather than as comparable to the well-sampled entries above.

Breed Estimate n tested
Norfolk Terrier 76.5% 17
Broholmer 75.0% 10
English Toy Spaniel 75.0% 2
Bergamasco 50.0% 1
Poodle Medium 50.0% 1
Portuguese Pointer 50.0% 1
Terrier Brazileiro 30.0% 5
Sealyham Terrier 25.0% 4
Caucasian Shepherd Dog 23.2% 41
Pyrenean Mastiff 20.0% 10
Wirehaired Vizsla 16.7% 3
Komondor 14.3% 14
Borzoi 13.8% 40
Czechoslovakian Wolfdog 12.5% 4
Lakeland Terrier 12.5% 8
American Hairless Rat Terrier 12.2% 37
German Hunting Terrier 11.5% 13
Tibetan Spaniel 11.5% 39
Australian Terrier 11.1% 9
Stabyhoun 11.1% 27
Coonhound Black And Tan 10.0% 5
Norwich Terrier 8.8% 17
Irish Terrier 8.6% 35
American Water Spaniel 8.3% 6
Finnish Hound 8.3% 36
Korean Jindo 8.3% 12
Nordic Spitz 8.3% 6
Eurasier 7.9% 19
Kerry Blue Terrier 7.1% 7
Kuvasz 7.1% 7
Silky Terrier 7.1% 28
Welsh Terrier 7.1% 21
Mcnab 3.6% 28
Lapponian Herder 1.9% 26
German Pinscher 1.7% 30
Lacy Dog 1.6% 32

128 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Scope of this record

Scope

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:000263-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:000263-9615 · Donner et al. 2023 · gnomAD v4.1 (Karczewski 2020) · ClinVar (Landrum 2018)